Palladium-Catalyzed α-Arylation of Vinylogous Esters for the Synthesis of γ,γ-Disubstituted Cyclohexenones

Abstract

A palladium-catalyzed α-arylation of cyclic vinylogous esters to form products that are converted in one step to γ-alkyl-γ-aryl-substituted cyclohexenones is reported. This Pd-catalyzed reaction proceeds at room temperature, is generally high-yielding, and uses an amount of a commercially available catalyst as low as 0.25 mol %. The scope of aryl bromides is particularly broad, and alkenyl bromides can also be used. This two-step protocol, comprising α-arylation and reductive transposition, can be performed in one pot and is applicable to gram-scale synthesis.

Challenging the Molecular Parameters of Vetiver: Can 4,5‐Dimethyl‐3‐(3′‐methylbut‐1′‐en‐2′‐yl)‐4‐phenylcyclopent‐2‐en‐1‐one Mimic Zizaenones in Structure and Odor?

“…Subjecting 13 to 12.5 mol-% nitro-Grela catalyst in refluxing toluene for 27 h provided in 53 % yield the TBS-protected 5-phenyl-3-isopropyl-4-methylenecyclohex-2-en-1-ol 16. [38] Next, we implemented a Pd-catalyzed α-arylation, recently reported by Lautens and co-workers, [38] to transform the 3-ethoxy-5-methylcyclopent-2-en-1-one (21) into the corresponding 5-methyl-5-phenyl-substituted ethoxy cyclopentenone 22. Instead of first reacting with the vinyl group of 13, the Grela catalyst 14 forms the ruthenium carbene 15, which then closes to a 6-membered ring with the vinyl carbinol substituent.…”

“…Unless otherwise stated, reagents and solvents (puriss. [38] At room temp., EtOH (48 mL) was added to a suspension of cyclopentane-1,3-dione (20; 10.0 g, 102 mmol, 1.00 eq.) Purification of the reaction products was carried out on a Biotage Isolera One Spektra System with an Accelerated Chromatographic Isolation (ACI) using SNAP Ultra (Ultra-Fast Flash Chromatography) Cartridges packed with HP-Sphere spherical silica, 25 μm.…”

“…TLC analyses were performed on Merck Kieselgel 60 F254 (particle size 5-20 μm, layer thickness 250 μm on glass, 10 cm × 10 cm) employing phosphomolybdic acid spray (Merck 1.00480.0100) as visualization reagent. [38] At -78°C under a N 2 atmosphere, a 2.5 M solution of nBuLi in hexanes (17.4 mL, 43.4 mmol) was slowly added to a solution of diisopropylamine (6.33 mL, 44.0 mmol) in THF (20 mL). IR spectroscopic data were recorded on a Bruker Alpha Platinum instrument with integrated diamond ATR.…”

“…Melting points (Mp) were determined on a Büchi melting point apparatus B 545 (uncorr.). 34 [38] At -20°C, a solution of 3-ethoxy-5-methylcyclopent-2-enone (21, 1.50 g, 10.7 mmol, 1.00 equiv.) NMR experiments were performed on Bruker Avance III HD 400 MHz, a Bruker Avance I 500 MHz, or a Bruker Avance II 600 MHz/ TCI 1.7 mircocryoprobe spectrometer in CDCl 3 or C 6 D 6 , as indicated.…”

α-C(sp3)-H Arylation of Cyclic Carbonyl Compounds

“…In which, cyclic vinylogous ester (3-or β-alkoxyl substituted cyclic α, β-unsaturated ketone) is more electron-rich thereby its dienolate is hardly formed by deprotonation. Furthermore, the dienolates are easy to polymerize with itself, further To overcome the limitation of aryl sources in this reaction, Lautens et al screened different palladium catalysts, and finally found that products (83a-83f) could be generated with high yield using the Palladium precatalyst Pd-P(tBu) 3 -G2, and α′ arylation could be realized at room temperature (Scheme 31) [82]. The α′-arylation of 3-ethoxy-2-cyclohexenone can also be effectively promoted by using the bulky base [83] or phosphine ligand with large steric hindrance [84].…”